title: Frequent infection of neurons by SV40 virus in SIV-infected macaque monkeys with progressive multifocal leukoencephalopathy and meningoencephalitis.
abstract: Simian virus 40 (SV40), family Polyomaviridae, in immunocompromised macaques can cause fatal demyelinating central nervous system disease analogous to progressive multifocal leukoencephalopathy caused by John Cunningham (JC) virus in immunocompromised humans. Recently, we have demonstrated that JC virus can infect cerebellar granule cell neurons and cortical pyramidal neurons in immunosuppressed people. To examine whether SV40 neuronal infection occurs spontaneously in immunosuppressed macaques, we analyzed archival brain specimens from 20 simian immunodeficiency virus-infected rhesus with AIDS and 1 cynomolgus post-transplant selected with SV40 brain infection from archival records from 1991 to 2012. In addition to white matter SV40 distribution in classic demyelinating progressive multifocal leukoencephalopathy, some of the 21 monkeys exhibited meningeal, subpial neocortical, and periventricular virus. This distribution pattern corresponded to broader viral tropism with neuronal infection in 14 (66.7%) of 21 cases. In all 14 cases, identified neurons were positive for early SV40 transcript large T antigen, but only 4 of the 14 cases exhibited late viral transcript viral protein 1-positive neurons. SV40-infected neurons were detected in frontal, parietal, occipital, and temporal cortices, hippocampus, thalamus, and brain stem. These observations confirm that spontaneous SV40 neuronal infection occurs in immunosuppressed macaques, which parallels JC virus-neuronal infection in immunosuppressed patients. Neuronal infection may be an important aspect of both SV40 and JC virus neuropathogenesis in their respective hosts.
authors.affiliation: Department of Comparative Pathology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Kaliyaperumal
authors.affiliation: Division of NeuroVirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Xin
authors.initials: X
authors.lastname: Dang
authors.affiliation: Division of NeuroVirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Christian
authors.initials: C
authors.lastname: Wuethrich
authors.affiliation: Department of Comparative Pathology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Knight
authors.affiliation: Department of Comparative Pathology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts.
authors.forename: Christine
authors.initials: C
authors.lastname: Pearson
authors.affiliation: Department of Comparative Pathology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts.
authors.forename: John
authors.initials: J
authors.lastname: MacKey
authors.affiliation: Novartis, Cambridge, Massachusetts.
authors.forename: Keith G
authors.initials: KG
authors.lastname: Mansfield
authors.affiliation: Division of NeuroVirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Igor J
authors.initials: IJ
authors.lastname: Koralnik
authors.affiliation: Department of Comparative Pathology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts. Electronic address: susan_westmoreland@hms.harvard.edu.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Westmoreland
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D060085:Coinfection / Q000378:metabolism / Q000473:pathology; D056784:Leukoencephalopathies / Q000378:metabolism / Q000473:pathology; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008590:Meningoencephalitis / Q000378:metabolism / Q000473:pathology; D027601:Polyomavirus Infections / Q000378:metabolism / Q000473:pathology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism / Q000473:pathology; D015302:Simian Immunodeficiency Virus; D013539:Simian virus 40; D014412:Tumor Virus Infections / Q000378:metabolism / Q000473:pathology